In chronic renal disease, the portions of the kidney which are relatively undamaged are responsible for maintaining the function of the organ; yet deterioration often ensues, even in the absence of evidence of activity of the primary disease. Similarly, in experimental renal insufficiency induced by subtotal nephrectomy in the rat, there is initially good compensation; later there is progressive deterioration with hypertension, azotemia, and apparently abnormal glomerular permeability with increasing proteinuria. It is the objective of this study to obtain ultrastructural data concerning the change in the glomerular filter accompanying the progression of renal failure and proteinuria in this system. As the permeability changes accompanying proteinuric states may involve both basement membranes and the podocyte foot processes, the permeability of both slitpores and of basement membrane will be studied with the probe molecules catalase and ferritin. Since, moreover, increased glomerular permeability to large molecules may be associated with reduced permeability to small molecules, we propose to study the capillary surface area and the slitpore area by morphometric methods, and the surface coat of the podocyte foot processes and the slit diaphragm by ultrastructural cytochemical techniques, including a method by means of which Rodewald and Karnovsky, at Harvard Medical School, have resolved a unique sieve-like substructure in the slit diaphragm. These studies are expected to give a better understanding of the pathogenesis and mechanism of one variety of glomerular disease associated with proteinuria, that of chronic renal failure in which the functional compensation of residual intact nephrons is not maintained, but seems rather to compromise the integrity of the surviving nephrons and their glomeruli.